UAB Researchers Explore Causes, Prevention

By Matt Windsor

Is suicide inevitable once the thoughts begin? Many fixate on this final solution to their problems long before they carry it out. Friends, family, and doctors often can do little to change this destructive thinking pattern. Few effective drugs are available, and all therapies can take weeks to have an effect.

“After a suicide attempt, many patients are just sent home, but they’re still at risk,” says Richard Shelton, M.D., Charles B. Ireland Professor of Psychiatry and vice chair for research in the UAB Department of Psychiatry and Behavioral Neurobiology. “Or they may be admitted to the hospital for three to five days, but we know that suicidal people don’t get well in a few days.”

Cheryl McCullumsmith

UAB researchers are now studying an entirely new approach—using intravenous infusions of the drug ketamine to short-circuit the cycle of negative thoughts that leads to suicide and provide a potentially lifesaving mood boost.

“Most suicide studies look at patients after they have made an attempt,” says Cheryl McCullumsmith, M.D., Ph.D., an assistant professor in the psychiatry department and president of the Alabama chapter of the American Foundation for Suicide Prevention. “We wanted to look at real patients presenting in the emergency room after suicide attempts or with suicidal thoughts.” McCullumsmith and Shelton are working with Henry Wang, M.D., and Janyce Sanford, M.D., of the UAB Department of Emergency Medicine, and a research team at Yale University on the project.

Rapid Relief

Ketamine has been used as an anesthetic and sedative for years, but newer research revealed that is also has a rapid antidepressant effect. “If you use doses that are much lower than what is required to put people to sleep, you can bring their mood up fairly rapidly,” Shelton says.

“In some people, it can seriously decrease suicidal thoughts for up to a week,” adds McCullumsmith. “That should open up a window of time to allow therapeutic interventions and other medicines to start working.”

Ketamine seems to elevate mood by boosting the synaptic connections between brain cells, McCullumsmith explains. “We’re very excited about this, because very few psychiatric medications, including none of the antidepressants, have been shown definitively to decrease suicide risk.” The only exception is lithium, which is used to treat bipolar disorder and also appears to decrease suicidality, she says. In fact, psychiatrists are now prescribing lithium along with antidepressants for some patients.

A Different Approach

"People get stuck in one way of thinking," McCullumsmith says. "I tell my patients, 'It's like you have blinders on that get narrower every week.'"

Up until fairly recently, “suicide has never been addressed as its own entity,” McCullumsmith explains. “People saw it as the end result of another condition, rather than as a separate phenomenon, but now we’re rethinking that.”

Depression is clearly a major risk factor, but it is not the only one, McCullumsmith says. “There are a lot of people who are very depressed but never suicidal, and a lot of people who are not that depressed but chronically suicidal, so there is more going on.”

One key component is the loss of cognitive flexibility. “People get stuck in one way of thinking,” McCullumsmith says. “I tell my patients, ‘It’s like you have blinders on that get narrower every week.’ Many of the people we see in the emergency room just can’t get these thoughts of suicide out of their heads, so they come in or their family members bring them in.”

Another element is hopelessness, “which is separate from depression,” McCullumsmith says. “They often go together, but not always.” The financial crisis of the past several years has dramatically increased hopelessness, she says. “You lose your job, and it creates a crisis of hopelessness, along with a loss of cognitive flexibility and a rise in impulsivity.”

Preliminary data suggests that people who are impulsive are much more likely to have a suicide attempt. The connection did not emerge in previous suicide studies because they generally focus on “clean” patients—excluding people who have a history of using or abusing drugs and alcohol. “But both increase your impulsivity significantly,” McCullumsmith says. “And people who use alcohol and drugs have a significantly higher risk of suicide attempts.”

Disrupting the Cycle

Many people think that a person who attempts suicide and fails has “gotten it out of their system,” but in fact, “once you’ve made an attempt, you’re much more likely to have another attempt,” McCullumsmith says. “Suicide attempts get very repetitive; they put a groove into people’s thinking patterns.”

Many people dealing with suicidal thoughts don’t seek help, but it is possible to escape, McCullumsmith emphasizes. Cognitive behavioral therapy helps disrupt negative thought patterns. “Antidepressants help make your thoughts less sticky, too,” she says. “They free up your brain to other ways of thinking. The combination of therapy and medicine works very well, but it can take six to eight weeks to start working.”

That’s why the ketamine study has such potential, McCullumsmith says. “If we can give people a break from these thoughts and, get them feeling better, we think we can really help.”